Last update 01 Nov 2024

HVCN1

Last update 01 Nov 2024

Basic Info

Synonyms

HV1, HVCN1, hydrogen voltage gated channel 1

+ [5]

Introduction

Mediates the voltage-dependent proton permeability of excitable membranes. Forms a proton-selective channel through which protons may pass in accordance with their electrochemical gradient. Proton efflux, accompanied by membrane depolarization, facilitates acute production of reactive oxygen species in phagocytosis.

Drugs associated with HVCN1

YHV98-4

Target

HVCN1

Mechanism

HVCN1 blockers

Active Org.

West China Hospital [+1]

Originator Org.

West China Hospital [+1]

Active Indication

Inflammatory pain

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ClGBI

Target

HVCN1

Mechanism

HVCN1 blockers

Active Org.

University of Debrecen

Originator Org.

University of Debrecen

Active Indication-

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CN114146175

Patent Mining

Target

HVCN1

Mechanism-

Active Org.

Zhejiang University

Originator Org.

Zhejiang University

Active Indication

Nervous System Diseases

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with HVCN1

100 Translational Medicine associated with HVCN1

0 Patents (Medical) associated with HVCN1

312

Literatures (Medical) associated with HVCN1

01 Oct 2024·Current Medicinal Chemistry

Role of S100 and YKL40 on Intraventricular Cerebral Hemorrhages in the Preterm Infant and the Neuroprotective Role of miR-138- siRNAs-HIF-1a and miR-21-siRNAs-HVCN1 in Neonatal Mice with Nerve Injury

Article

Author: Moradi-Sardareh, Hemen ; Ijabi, Janat ; Ijabi, Roghayeh ; Kaminsky, Zachary A. ; Roozehdar, Parisa ; Tehranian, Najmeh

Background:Epilepsy and intraventricular-cerebral hemorrhage is a common complication irreversible in preterm infants. Inflammation leads to an increase in intracellular calcium, acidosis, and oxygen usage, and finally, may damage brain cells. Increases in HIF-1a and HVCN1 can reduce the complications of oxygen consumption and acidosis in infants with intraventricular hemorrhage (IVH). On the other hand, decreases in S100B can shield nerve cells from apoptosis and epilepsy by reducing brain damage.Objective:In this research, we investigated how miR-138-siRNAs-HIF-1a and miR-21- siRNAs-HVCN1 affect apoptosis in hypoxic mice.Methods:On the first and third days after delivery, the YKL40, HIF-1a, HVCN1, and S100b genes were compared between two groups of preterm infants with and without maternal inflammation. Afterward, the miRNAs were transfected into cell lines to monitor variations in YKL40, HIF-1a, HVCN1, and S100b gene expression and nerve cell apoptosis. We changed the expression of S100b, HVCN1, and HIF-1a genes by using specific siRNAs injected into mice. Using real-time PCR, Western blotting, flow cytometry (FCM), and immunofluorescence, and changes in gene expression were evaluated (IHC).Results:HVCN1 gene expression showed a strong negative correlation with epilepsy in both groups of infants (P< 0.001). Significant correlations between epilepsy and the expression levels of the S100b, YKL40, and HIF-1a genes were found (P< 0.001). According to FCM, after transfecting miRNA-431 and miRNA-34a into cell lines, the apoptosis index (A.I.) were 41.6 3.3 and 34.5 5.2%, respectively, while the A.I. were 9.6 2.7 and 7.1 4.2% after transfecting miRNA-21 and miRNA-138. MiR-138-siRNAs-HIF-1a and miR-21-siRNAs-HVCN1 were simultaneously injected into hypoxic mice, and IHC double-labeling revealed that this reduced apoptosis and seizures compared to the hypoxic group.Results:HVCN1 gene expression showed a strong negative correlation with epilepsy in both groups of infants (P< 0.001). Significant correlations between epilepsy and the expression levels of the S100b, YKL40, and HIF-1a genes were found (P< 0.001). According to FCM, after transfecting miRNA-431 and miRNA-34a into cell lines, the apoptosis index (A.I.) were 41.6 3.3 and 34.5 5.2%, respectively, while the A.I. were 9.6 2.7 and 7.1 4.2% after transfecting miRNA-21 and miRNA-138. MiR-138-siRNAs-HIF-1a and miR-21-siRNAs-HVCN1 were simultaneously injected into hypoxic mice, and IHC double-labeling revealed that this reduced apoptosis and seizures compared to the hypoxic group.Conclusion:Our findings demonstrate that miR-138-siRNAs-HIF-1a and miR-21-siRNAs- HVCN1 injections prevent cerebral ischemia-induced brain damage in hypoxia mice by increasing HVCN1 and HIF-1a and decreasing S100b, which in turn lessens apoptosis and epilepsy in hypoxic mice.

01 Aug 2024·Inflammopharmacology

Honokiol alleviates monosodium urate-induced gouty pain by inhibiting voltage-gated proton channels in mice

Article

Author: Yuan, Ziqi ; Miao, Lurong ; Zhang, Shijia ; Zhang, Guangqin

OBJECTIVETo investigate whether honokiol (HNK) acted as an analgesic in connection with inhibiting the voltage-gated proton channel (Hv1).METHODSThe model of gouty arthritis was induced by injecting monosodium urate (MSU) crystals into the hind ankle joint of mice. HNK was given by intragastric administration. Ankle swelling degree and mechanical allodynia were evaluated using ankle joint circumference measurement and von Frey filaments, respectively. Hv1 current, tail current, and action potential in dorsal root ganglion (DRG) neurons were recorded with patch-clamp techniques.RESULTSHNK (10, 20, 40 mg/kg) alleviated inflammatory response and mechanical allodynia in a dose-dependent manner. In normal DRG neurons, 50 µM Zn²⁺ or 2-GBI significantly inhibited the Hv1 current and the current density of Hv1 increased with increasing pH gradient. The amplitude of Hv1 current significantly increased on the 3rd after MSU treatment, and HNK dose-dependently reversed the upregulation of Hv1 current. Compared with MSU group, 40 mg/kg HNK shifted the activation curve to the direction of more positive voltage and increased reversal potential to the normal level. In addition, 40 mg/kg HNK reversed the down-regulation of tail current deactivation time constant (τ_tail) but did not alter the neuronal excitability of DRG neurons in gouty mice.CONCLUSIONHNK may be a potential analgesic by inhibiting Hv1 current.

01 Aug 2024·Biophysical Journal

Zinc inhibits the voltage-gated proton channel HCNL1

Article

Author: Berger, Thomas K ; Kuwabara, Makoto F. ; Klemptner, Joschua ; Muth, Julia ; Berger, Thomas K. ; Oliver, Dominik ; De Martino, Emilia ; Kuwabara, Makoto F

Voltage-gated ion channels allow ion flux across biological membranes in response to changes in the membrane potential. HCNL1 is a recently discovered voltage-gated ion channel that selectively conducts protons through its voltage-sensing domain (VSD), reminiscent of the well-studied depolarization-activated Hv1 proton channel. However, HCNL1 is activated by hyperpolarization, allowing the influx of protons, which leads to an intracellular acidification in zebrafish sperm. Zinc ions (Zn²⁺) are important cofactors in many proteins and essential for sperm physiology. Proton channels such as Hv1 and Otopetrin1 are inhibited by Zn²⁺. We investigated the effect of Zn²⁺ on heterologously expressed HCNL1 channels using electrophysiological and fluorometric techniques. Extracellular Zn²⁺ inhibits HCNL1 currents with an apparent half-maximal inhibition (IC₅₀) of 26 μM. Zn²⁺ slows voltage-dependent current kinetics, shifts the voltage-dependent activation to more negative potentials, and alters hyperpolarization-induced conformational changes of the voltage sensor. Our data suggest that extracellular Zn²⁺ inhibits HCNL1 currents by multiple mechanisms, including modulation of channel gating. Two histidine residues located at the extracellular side of the VSD might weakly contribute to Zn²⁺ coordination: mutants with either histidine replaced with alanine show modest shifts of the IC₅₀ values to higher concentrations. Interestingly, Zn²⁺ inhibits HCNL1 at even lower concentrations from the intracellular side (IC₅₀ ≈ 0.5 μM). A histidine residue at the intracellular end of S1 (position 50) is important for Zn²⁺ binding: much higher Zn²⁺ concentrations are required to inhibit the mutant HCNL1-H50A (IC₅₀ ≈ 106 μM). We anticipate that Zn²⁺ will be a useful ion to study the structure-function relationship of HCNL1 as well as the physiological role of HCNL1 in zebrafish sperm.

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HVCN1

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